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Identifying 2PHDO as a SOCE Inhibitor from Chinese Herbal Extracts
Jindou Liu1, Hao Deng2,3,4, Yaxin Li1
1Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
Current Pharmaceutical Biotechnology
|June 15, 2023
Summary
Researchers discovered 2PHDO, a novel inhibitor of store-operated calcium entry (SOCE), from Chinese herbal medicine. This compound effectively blocks SOCE and may serve as a template for new therapeutics targeting SOCE-related diseases.
Area of Science:
- Biochemistry
- Pharmacology
- Immunology
Background:
- Store-operated calcium entry (SOCE) is vital for immune, muscle, and neuronal functions.
- Developing specific SOCE inhibitors is crucial for treating related disorders but remains challenging.
Purpose of the Study:
- To identify novel SOCE inhibitors from Chinese herbal extracts.
- To investigate the mechanism of action of a newly identified inhibitor.
Main Methods:
- Screening of Chinese herbal extracts for SOCE inhibitory activity.
- Characterization of inhibitor potency, specificity, and mechanism using cellular assays.
- Investigated STIM1 and Orai1 interactions.
Main Results:
- Identified 2PHDO, a novel SOCE inhibitor, from herbal extracts.
- 2PHDO inhibits SOCE and NFAT translocation in various cell types with IC50 around 1 µM.
- 2PHDO specifically targets Orai1, without affecting STIM1 activation or STIM1-Orai1 coupling.
Conclusions:
- 2PHDO is a potent and specific SOCE inhibitor.
- 2PHDO can serve as a lead compound for developing new drugs for SOCE-related diseases.
- Screening herbal medicine is a feasible strategy for discovering novel SOCE inhibitors.
